Clinical trial: a single‐centre, randomised, controlled trial of tradipitant on satiation, gastric functions, and serum drug levels in healthy volunteers. Issue 2 (29th May 2022)

• Record Type: Journal Article
• Authors: Khanna, Lehar; Zheng, Ting; Atieh, Jessica; Torres, Monique; Busciglio, Irene; Carlin, Jesse L.; Xiao, Michael; Harmsen, William S.; Camilleri, Michael
• Is Part Of: Alimentary pharmacology & therapeutics. Volume 56:Issue 2(2022)
• Page Start: 224
• Page End: 230
• Publication Date: 2022-05-29
• Subjects: accommodation -- gastric emptying -- neurokinin -- receptor -- volume; Digestive organs -- Diseases -- Treatment -- Periodicals; Digestive organs -- Effect of drugs on -- Periodicals; Gastrointestinal system -- Diseases -- Treatment -- Periodicals; Gastrointestinal system -- Effect of drugs on -- Periodicals; 615.73
• DOI: 10.1111/apt.17065
• Languages: English
• ISSNs: 0269-2813

Abstract

Summary: Background: Tradipitant, an NK1 receptor antagonist, improved symptoms in patients with gastroparesis. It is unclear whether these effects are mediated centrally (e.g., vomiting centre) or on gastric functions. As a class, NK1 antagonists may retard gastric emptying (GE) or increase fasting and postprandial gastric volumes (GV). Aim: To evaluate the effects of tradipitant relative to placebo on gastric motor functions, satiation, postprandial symptoms, and pharmacokinetics. Methods: We conducted a randomised, double‐blind, placebo‐controlled, single‐centre study of tradipitant 85 mg or matching placebo b.i.d. for 9 consecutive days in 24 healthy volunteers. During the last 2 days of treatment, participants underwent scintigraphic measurements of GE of 320 kcal egg meal, fasting and postprandial GV by SPECT, and satiation by nutrient drink ingested to maximum tolerated volume (MTV) and symptoms 30 min later. Treatments were compared by Wilcoxon rank sum test. The study had 80% power to detect group differences of 23.6% in GV and 29.2% in GE T1/2 . Results: The two groups of healthy participants were well balanced based on demographic features, age, and BMI. There were nonsignificant positive correlations between blood levels of tradipitant and accommodation GV and GE at 4 h. There were no significant effects of tradipitant, 85 mg b.i.d. for 9 days compared to placebo on GE, GV, satiation, or symptoms 30 min after MTV. Conclusion: Tradipitant, 85 mg b.i.d., does not significantly affect gastric motor functions (GV or GE). Importantly, there was no retardation of GE by tradipitant, which is important in relation to its potential use in patients with gastroparesis. Clinic trials registry: ClinicalTrials.gov #NCT04849559. Abstract : Tradipitant, an NK1 receptor antagonist, has shown improvement in nausea and vomiting in patients with gastroparesis. NK1 receptors are located invomiting centre and myenteric neurons; an NK1 antagonist may inhibit GI motor functions. What is the effect of tradipitant on the motor functions of the human stomach?